Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells

Shujuan Jiang, Sean Christopher Dowdy, Xue W. Meng, Zhaoyu Wang, Monica B. Jones, Karl C. Podratz, Shi Wen Jiang

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective.: To characterize the molecular pathways involved in apoptosis following administration of histone deacetylase inhibitors to Type I and II endometrial cancer cells. Methods.: Ark2, Ishikawa, and AN3 cell lines representing both Type I and II endometrial cancers were treated with various concentrations of oxamflatin and HDAC inhibitor-1. Cell apoptosis was determined by flow cytometry, nuclear staining, Western blotting, and mitochondrial membrane potential assays. Results.: Compared to controls, there was a 95% reduction in the growth of Ark2 cells following administration of histone deacetylase inhibitors and this response was dose-dependent. These agents also caused profound morphologic changes and loss of mitochondrial membrane potentials consistent with the induction of apoptosis. Cleavage of PARP, caspase-9, and caspase-8 was detected, confirming the activation of apoptotic cascades in endometrial carcinoma cells. This effect was present in both serous and endometrioid cell types. Conclusion.: Our results suggest that oxamflatin and HDAC inhibitor-1 have potent cytotoxicity in endometrial cancer cells by inducing cell apoptosis. Histone deacetylase inhibitors are promising agents for the treatment of both Type I and II endometrial carcinoma.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalGynecologic Oncology
Volume105
Issue number2
DOIs
StatePublished - May 2007

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Histone Deacetylase Inhibitors
Endometrial Neoplasms
Apoptosis
Mitochondrial Membrane Potential
Caspase 9
Caspase 8
Flow Cytometry
Western Blotting
Staining and Labeling
Cell Line
Growth

Keywords

  • Apoptosis
  • Endometrial cancer
  • Histone deacetylase

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells. / Jiang, Shujuan; Dowdy, Sean Christopher; Meng, Xue W.; Wang, Zhaoyu; Jones, Monica B.; Podratz, Karl C.; Jiang, Shi Wen.

In: Gynecologic Oncology, Vol. 105, No. 2, 05.2007, p. 493-500.

Research output: Contribution to journalArticle

Jiang, Shujuan ; Dowdy, Sean Christopher ; Meng, Xue W. ; Wang, Zhaoyu ; Jones, Monica B. ; Podratz, Karl C. ; Jiang, Shi Wen. / Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells. In: Gynecologic Oncology. 2007 ; Vol. 105, No. 2. pp. 493-500.
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